Regeneration: Acute necrosis and degeneration of rat pancreas acinar cells is produced by protein-deficient diet and ethionine injection for 10 days. During the next 18 days, regeneration and full restitution of the gland from less than 10% to 100% occurs on a stock diet with discontinuance of ethionine. This regenerative capacity makes it equivalent to that of liver follwing partial hepatectomy. This model system has been studied morphologically and enzymatically. Present studies are concerned with changes in histone labeling and histone side chain modification, acetate, methyl, phosphate, during regeneration using labeled substrates. These studies are being extended to include nonhistone nuclear protein changes during regeneration. Differentiation: We have shown it possible to culture embryonic pancreas in a chemically defined medium for periods up to 10 weeks. By periodic subdivision of tissue, mass increments of 1000X are achieved without major modification of structure or function. Studies are being conducted to show long term effects of methionine restriction, effects of chemical carcinogens and BUDR.